Agricultural workers are an occupational sector particularly vulnerable to heat-related illness. Occupational exposure to heat can result in injuries, disease, reduced productivity, and death and these risks have been well documented in NIOSH priority documents on occupational exposure to heat and hot environments. In addition to these known heat-related health threats, in recent years researchers have theorized that hot environmental temperatures and strenuous work may play a role in the development of chronic kidney disease of unknown etiology (CKDu), a disease that strikes young otherwise healthy, agricultural workers, and has been reported in many tropical countries and resulted in tens of thousands of deaths. The burden of chronic kidney disease is growing globally with increasing incidence and prevalence of individuals requiring replacement therapy, with poor outcomes and high cost. Among agricultural workers, it has been hypothesized that heat exposure, dehydration, volume depletion, and the combination of heat and/or other exposures may play a role in the development of decreased renal function. Most of the studies of CKDu have been conducted on agricultural workers in Central America and other countries with rising environmental temperatures. Our current research on physiologic response to heat among agricultural workers in Florida has revealed that of the workers start their workday with concentrated urine, and 3 of them end their workday in this state and that among 192 workers followed over the course of 2-3 workdays, 33% had serum creatinine increases indicative of acute kidney injury (AKI) on at least one workday. The most significant predictor for AKI was increase in heat index. Motivated by these intriguing observations and in alignment with the NIOSH strategic priority to reduce chronic disease in workers, we propose to recruit and study a cohort of 90 Florida agricultural workers over a two year period to examine the inter-relationships between environmental heat exposure, biomarkers of renal function, persistence of AKI and indicators of renal function degradation. Specifically, we aim to: 1) Determine if renal biomarkers, AKI, and sustained decrease in renal function are associated with environmental and exertional heat exposure in heat-exposed agricultural workers over two years; 2) Use non-targeted metabolomic analysis to explore physiologic pathways of AKI and degradation of renal function in agricultural workers; 3) Determine if exposure to pesticides commonly used on Florida crops are independently associated or modify observed changes in renal function, and if these relationships are modified by factors such as smoking and pain medication use; and 4) Using an r2p approach, develop an educational intervention toolkit for workers and other relevant stakeholders (e.g., health care providers and agricultural employers) aimed to promote hydration and healthy renal function. The outputs and outcomes of this study will yield key information on workers physiological response to heat and lead to the development of interventions and policies to protect the long-term health of agricultural workers and other vulnerable populations.